Background: Thiamethoxam (THM) is a neonicotinoid insecticide used to control different insect pests on fruits, vegetables, and field crops. The misuse and continuous exposure to THM cause many harmful effects on health and the reproductive system. Aim: This work aims to investigate the efficiency of vitamin C (vit C) in reducing or eliminating the harmful effects of THM on the testes, liver, and kidney of male rats. Methods: Forty-eight sexually mature male Wister albino rats (weight: 170–190 g; age: 10–11 weeks) were randomly allocated into six groups (8 males/group). The control group was orally given distilled water, vit C group was orally treated with 200 mg/kg b.wt of vit C, group 1/10 of THM LD50 orally treated with 156.3 mg/kg b.wt of THM, group 1/20 of THM LD50 orally treated with 78.15 mg/kg b.wt of THM, group 1/10 of THM LD50 + vit C orally treated with 156.3 mg/kg b.wt of THM + 200 mg/kg b.wt of vit C, and group 1/20 of THM LD50 + vit C orally treated with 78.15 mg/kg b.wt of THM + 200 mg/kg b.wt of vit C. All groups were treated for five days per week for a whole period of 58 days. Blood samples were collected at the end of the experiment, and serum was extracted for liver and kidney functions and antioxidant measurements. Reproductive organs (testis, epididymis, and seminal vesicles) were collected and weighed at the end of the experiment. Results: The results showed that groups exposed to 1/10 and 1/20 of THM LD50 significantly (p < 0.05) decreased the body weight, the reproductive organ weights (testis, epididymis, and seminal vesicles), spermatid count, sperm (count and motility), and testosterone concentration with an increase in abnormalities. In addition, the groups exposed to THM showed a decrease in protein concentration, albumin, and globulin, and caused an increase in glucose concentration. The activities of alkaline phosphatase (ALP), alanine transaminase (ALT), aspartate transaminase (AST), creatinine, urea, and malondialdehyde (MDA) were increased while caused decrease in total antioxidant capacity (TAC) due to exposure to THM. The co-administration of vit C with HM modulated the harmful effects of the insecticide on testicular, liver, and kidney parameters, which confirmed in histopathological examination of testis. Groups orally treated with vit C showed a significant increase in spermatogenesis, spermatid numbers, and the weight of seminal vesicles. Conclusion: This study showed the importance of vit C in reducing toxic effects from exposure to THM. Accordingly, the intake of vit C by individuals who regularly handle this insecticide will be beneficial in reducing the adverse effects that may occur in the liver and kidney.